Rapamycin 42-esters are derivatives of rapamycin, a macrocyclic triene antibiotic produced naturally by Streptomyces hygroscopicus. Rapamycin has been found useful in an array of applications based on its antitumoral and immunosuppressive effects. Such uses include preventing, inhibiting, or treating transplant rejection, graft vs. host disease, autoimmune diseases including systemic lupus erythematosis, inflammatory diseases including pulmonary and ocular inflammation, adult T cell leukemia/lymphoma, solid tumors, fungal infections, and hyperproliferative vascular disorders, including smooth muscle cell proliferation and intimal thickening following vascular surgery. Rapamycin and rapamycin derivatives, including rapamycin 42-esters such as rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid (CCI-779), continue to be studied for treatment of these and other conditions.
The preparation and use of 42-esters of rapamycin, including CCI-779, are described in U.S. Pat. No. 5,362,718. A regioselective synthesis of CCI-779 is described in U.S. Pat. No. 6,277,983. In US Patent Publication No. US 2005-0033046 A1 (also U.S. patent application Ser. No. 10/903,062), a regioselective synthesis of CCI-779 is described based on boronate chemistry.
What are needed are additional efficient methods of preparing a rapamycin 42-ester, including a scalable method for purifying the rapamycin 42-ester.